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Muscle Accrual and Function in Cystic Fibrosis-Impact of Glucose Intolerance

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ClinicalTrials.gov Identifier: NCT02776098
Recruitment Status : Recruiting
First Posted : May 18, 2016
Last Update Posted : December 21, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Brief Summary:
This study will investigate the link between glucose abnormalities and elements critical to muscle function including mass, composition and energy metabolism. the primary goal of the study is to determine whether Cystic Fibrosis (CF) disease is associated with muscle dysfunction, especially in the presence of glucose intolerance. This is a longitudinal cohort study of 3 main groups: CF subjects without Cystic Fibrosis-related diabetes (CFRD), healthy matched controls and CF subjects with newly diagnosed CFRD started on insulin therapy.

Condition or disease
Cystic Fibrosis

Detailed Description:

Cystic Fibrosis (CF) is a lethal inherited disease that primarily affects the lungs but also confers a high risk of diabetes, with up to 40-50% of adults experiencing Cystic Fibrosis-related diabetes (CFRD). CFRD is associated with an accelerated decline in lung function, nutritional status and survival and despite treatment mortality in patients with CFRD remains high. Airway inflammation and susceptibility to infections caused by hyperglycemia, and the catabolic effect of insulin deficiency are posited mechanisms of CFRD-associated morbidity. Respiratory failure caused by airway disease is well known but the contribution of respiratory muscle dysfunction may be critical. In Type 2 Diabetes Mellitus (T2DM) glucose and insulin defects are closely correlated with muscle function. The pulmonary muscles are crucial to respiration and airway clearance in CF. Muscle function is dependent on its mass, composition, and energy metabolism. Lean body mass (LBM) deficits are present in CF and improvement in LBM improves pulmonary function. Using T2DM as a model for muscle dysfunction, the study hypothesis is that glucose intolerance exacerbates LBM deficits, negatively affects muscle composition, and alters muscle metabolism leading to respiratory muscle dysfunction and a decline in pulmonary function.

CF subjects without CFRD and healthy controls will undergo 3 study visits (baseline then annually for 2 years) and CFRD subjects will undergo 2 study visits (baseline and 6 months after baseline). Evaluations will include neurologic exams, anthropometric assessments, 3-day dietary recall, MRI scans, oral glucose tolerance tests (CF subjects only), blood work, pulmonary function testing, muscle strength testing, exercise testing, bone density scans, and adverse event assessment.


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Study Type : Observational
Estimated Enrollment : 62 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Muscle Accrual and Function in Cystic Fibrosis-Impact of Glucose Intolerance
Study Start Date : May 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Group/Cohort
Cystic Fibrosis without Cystic Fibrosis-related Diabetes
Subjects with a confirmed diagnosis of Cystic Fibrosis (CF) without Cystic Fibrosis-related diabetes will be followed annually for 2 years for a total of four study visits over 2 years (screening, baseline, 12 and 24 month visits).
Newly Diagnosed Cystic Fibrosis-Related Diabetes
Subjects with a confirmed diagnosis of Cystic Fibrosis (CF) and new diagnosis of Cystic Fibrosis-Related Diabetes (CFRD) will be followed for a total of 3 study visits over 6 months (screening, baseline and 6 months).
Healthy Controls
Age, sex, ethnicity and body mass index matched (at time of enrollment to CF without CFRD subjects) healthy controls will be followed annually for 2 years for a total of four study visits (screening, baseline, 12 and 24 month visits).



Primary Outcome Measures :
  1. Compare change in mean lean body mass (LBM) from baseline to end of study [ Time Frame: 24 months (CF without CFRD subjects & healthy controls); 6 months for CF subjects ]

Secondary Outcome Measures :
  1. Compare Intramyocellular lipid (IMCL) accumulation from baseline to end of study [ Time Frame: 24 months (CF without CFRD subjects & healthy controls); 6 months for CF subjects ]
    Proton magnetic resonance spectroscopy will be used to measure IMCL per previously published methods.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

This is longitudinal cohort study of 3 main study groups: CF subjects without CFRD, Healthy matched controls and CF subjects with newly diagnosed CFRD started on insulin therapy. Healthy controls without CF will be recruited and will be matched for age, sex, ethnicity, and body mass index (BMI) to CF subjects. Subjects with newly diagnosed CFRD will also be enrolled. This study will be carried out over a 5-year period.

CF subjects without CFRD (26) and healthy controls (26) will be followed annually for 2 years. CF subjects with newly diagnosed CFRD (10) will be followed for 6 months.

Criteria

Inclusion Criteria for CF subjects without CFRD:

  1. Males or females age 16 to 22 years.
  2. Confirmed diagnosis of CF per CF Foundation guidelines
  3. Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria for CF subjects without CFRD

  1. Chronic systemic glucocorticoid use e.g. for allergic bronchopulmonary aspergillosis
  2. Organ transplantation
  3. Forced Expiratory Volume (FFEV) 1%-predicted < 40%
  4. Established diagnosis of CFRD and treatment with insulin or hypoglycemic agent
  5. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
  6. Pregnancy or breastfeeding (if female)
  7. Pre-existing neurological or neuromuscular disease

All study visits for CF subjects will be scheduled during periods of baseline health. Visits will not be performed within 4 weeks of an acute respiratory illness or pulmonary exacerbation.

Inclusion Criteria for healthy controls

  1. Age-, sex-, ethnicity-, and BMI-matched at time of enrollment to CF subjects without CFRD
  2. Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria for healthy controls

  1. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
  2. Pregnancy or breastfeeding (if female)
  3. Pre-existing neurological or neuromuscular disease

Inclusion Criteria for CF subjects with new CFRD

  1. Males or females age 12 years or above.
  2. Confirmed diagnosis of CF per CF Foundation guidelines.
  3. New diagnosis of CFRD based on a) a clinically indicated Oral glucose tolerance test (OGTT) b) hyperglycemia (PG>200 mg/dL) persisting >48 hours and/or c) elevated HbA1C and within 4 weeks of starting insulin therapy.
  4. Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria for CF subjects with new CFRD

  1. Chronic systemic glucocorticoid use e.g. for allergic bronchopulmonary aspergillosis
  2. Organ transplantation
  3. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
  4. Pregnancy or breastfeeding (if female)
  5. Pre-existing neurological or neuromuscular disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02776098


Contacts
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Contact: Saba Sheikh, MD 215-590-3749 sheikhs@email.chop.edu
Contact: Davina Laracuente LARACUENTD@email.chop.edu

Locations
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United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Saba Sheikh, MD    215-590-3749    sheikhs@email.chop.edu   
Contact: Davina Laracuente       LARACUENTD@email.chop.edu   
Principal Investigator: Saba Sheikh, MD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Davina Laracuente       LARACUENTD@EMAIL.CHOP.EDU   
Principal Investigator: Ravinder Reddy, MD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
National Institutes of Health (NIH)
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Saba Sheikh, MD Children's Hospital of Philadelphia

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Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT02776098     History of Changes
Other Study ID Numbers: 15-012279
1K23DK107937-01 ( U.S. NIH Grant/Contract )
First Posted: May 18, 2016    Key Record Dates
Last Update Posted: December 21, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Children's Hospital of Philadelphia:
Cystic Fibrosis
Glucose Intolerance
Muscle Accrual
Cystic Fibrosis-related Diabetes
Healthy Controls
Healthy Participants

Additional relevant MeSH terms:
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Fibrosis
Cystic Fibrosis
Glucose Intolerance
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases